Huang Xiaodong, Wang Xingxiu, Cheng Chun, Cai Jing, He Song, Wang Hua, Liu Fang, Zhu Changlai, Ding Zongmei, Huang Xianting, Zhang Tianyi, Zhang Yixin
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong University, Nantong.
APMIS. 2014 Nov;122(11):1070-9. doi: 10.1111/apm.12258. Epub 2014 May 26.
The development of molecular pathogenesis of hepatocellular carcinoma (HCC) is complex and involves alterations in the expression and conformation of assorted oncoproteins and tumor suppressors. Chaperonin containing TCP1 (CCT) is a cytolic molecular chaperone complex that is required for the correct folding of numerous proteins. In this study, we investigated a possible involvement of CCT subunit 8 (CCT8) in HCC development. Immunohistochemical analysis was performed in 102 human HCC samples. High CCT8 expression was detected in clinical HCC samples compared with adjacent noncancerous tissues. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. Western blot confirmed the high expression of CCT8 in HCC compared with adjacent normal tissue. Moreover, the biological significance of the aberrant expression of CCT8 was investigated in HCC cell lines. Expression of CCT8 was correlated directly with the histologic grades and tumor size of HCC and high expression of CCT8 was associated with a poor prognosis. CCT8 depletion by siRNA inhibited cell proliferation and blocked S-phase entry in HuH7 cells. These results suggested that CCT8 might be an oncogene and participate in HCC cell proliferation. These findings provide a potential therapeutic strategy for the treatment of HCC.
肝细胞癌(HCC)分子发病机制的发展是复杂的,涉及各种癌蛋白和肿瘤抑制因子的表达及构象改变。含TCP1的伴侣蛋白(CCT)是一种胞质分子伴侣复合物,众多蛋白质的正确折叠都需要它。在本研究中,我们调查了CCT亚基8(CCT8)在HCC发展中可能的作用。对102例人类HCC样本进行了免疫组织化学分析。与相邻的非癌组织相比,临床HCC样本中检测到CCT8高表达。还进行了单因素和多因素生存分析以确定其预后意义。蛋白质印迹法证实与相邻正常组织相比,HCC中CCT8高表达。此外,在HCC细胞系中研究了CCT8异常表达的生物学意义。CCT8的表达与HCC的组织学分级和肿瘤大小直接相关,CCT8高表达与预后不良相关。通过小干扰RNA(siRNA)使CCT8缺失可抑制HuH7细胞的增殖并阻止其进入S期。这些结果表明CCT8可能是一种癌基因并参与HCC细胞增殖。这些发现为HCC的治疗提供了一种潜在的治疗策略。